Recent developments in immunotherapy for gastrointestinal tract cancers

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 9, 2024

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. role immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in treatment advanced perioperative GI Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen unselected gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), esophageal (EC). In addition, encouraging performance claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy later-line cancers brings new hope cell solid tumour treatment. Nevertheless, remains yet precise, researchers are dedicated to further maximising optimising efficacy. This review summarises important research, latest progress, future directions including EC, G/GEJC, CRC.

Language: Английский

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Liver Metastases and Immune Checkpoint Inhibitor Efficacy in Patients With Refractory Metastatic Colorectal Cancer

JAMA Network Open, Journal Year: 2023, Volume and Issue: 6(12), P. e2346094 - e2346094

Published: Dec. 5, 2023

Importance Immune checkpoint inhibitors (ICIs) have limited activity in microsatellite-stable (MSS) or mismatch repair–proficient (pMMR) colorectal cancer. Recent findings suggest the efficacy of ICIs may be modulated by presence liver metastases (LM). Objective To investigate association between LM and ICI advanced MSS Design, Setting, Participants In this secondary analysis Canadian Cancer Trials Group CO26 (CCTG CO.26) randomized clinical trial, patients with treatment-refractory cancer were a 2:1 fashion to durvalumab plus tremelimumab best supportive care alone August 10, 2016, June 15, 2017. The primary end point was overall survival (OS) 80% power 2-sided α = .10. median follow-up 15.2 (0.2-22.0) months. post hoc performed from February 11 14, 2022, subgroups defined based on absence study treatments. Intervention Durvalumab care. Main Outcomes Measures Hazard ratios (HRs) 90% CIs calculated stratified Cox proportional hazards regression model. Plasma tumor mutation burden at entry determined using circulating DNA assay. OS, as time randomization death due any cause; points included progression-free (PFS) disease control rate (DCR). Results Of 180 enrolled (median age, 65 [IQR, 36-87] years; 121 [67.2%] men; 19 [10.6%] Asian, 151 [83.9%] White, 10 [5.6%] other race ethnicity), present 127 (70.6%). For LM, there higher proportion male (94 [74.0%] vs 27 53 [50.9%]; P .005), initial diagnosis shorter (median, 40 [range, 8-153] 56 14-181] months; .001). significantly LM. Patients without had improved PFS (HR, 0.54 [90% CI, 0.35-0.96]; .08; .02 for interaction). Disease 49% (90% 36%-62%) treated tremelimumab, compared 14% 6%-38%) those (odds ratio, 5.70 1.46-22.25]; .03). On multivariable analysis, OS Conclusions Relevance CCTG CO.26 study, associated worse outcomes DCR tremelimumab. Liver poor treatment should considered design interpretation future studies evaluating therapy.

Language: Английский

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Liver metastases do not predict resistance to the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab in proficient MMR metastatic colorectal cancer: a secondary analysis of the AtezoTRIBE study

ESMO Open, Journal Year: 2025, Volume and Issue: 10(2), P. 104135 - 104135

Published: Feb. 1, 2025

Language: Английский

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Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 10, 2025

Language: Английский

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Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(12), P. 839 - 851

Published: Sept. 24, 2024

Language: Английский

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Immunotherapy for Microsatellite-Stable Metastatic Colorectal Cancer: Can we close the Gap between Potential and Practice?

Current Oncology Reports, Journal Year: 2024, Volume and Issue: 26(10), P. 1258 - 1270

Published: July 30, 2024

This review will explore various strategies to rendering MSS mCRCs susceptible ICI. Moreover, we provide an overview of potential biomarkers that may aid better patient selection, and discuss ongoing efforts in this area research.

Language: Английский

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Third-line treatment and beyond in metastatic colorectal cancer: What do we have and what can we expect?

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 202, P. 104454 - 104454

Published: July 21, 2024

Language: Английский

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The long-term effectiveness and mechanism of oncolytic virotherapy combined with anti-PD-L1 antibody in colorectal cancer patient

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(9), P. 1412 - 1426

Published: July 27, 2024

Colorectal cancer (CRC) is known to be resistant immunotherapy. In our phase-I clinical trial, one patient achieved a 313-day prolonged response during the combined treatment of oncolytic virotherapy and To gain deeper understanding potential molecular mechanisms, we performed comprehensive multi-omics analysis on this three non-responders. Our investigation unveiled that, initially, tumor microenvironment (TME) responder presented minimal infiltration T cells natural killer cells, along with relatively higher presence macrophages compared Remarkably, treatment, there was progressive increase in CD4

Language: Английский

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Tislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 23, 2024

Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Mechanistic insights suggested that epidermal growth factor receptor (EGFR) antibody plus irinotecan might augment tumor immune response mCRC. Therefore, we conducted a proof-of-concept, single-arm, phase 2 study (ChiCTR identifier: ChiCTR2000035642) combination regimen including tislelizumab (anti-PD-1), cetuximab (anti-EGFR) and 33 patients with MSS RAS wild-type (WT) mCRC who were previously treated ≥2 lines therapy. The primary endpoint was met, confirmed objective rate 33%. As secondary endpoints, disease control 79%, median progression-free survival overall 7.3 17.4 months respectively. Among patients, 32 (97.0%) had treatment-related adverse events (AEs). Three (9.1%) reported grade ≥ 3 AEs, rash (n = 1), neutropenia 2). post-hoc evaluation dynamic circulating DNA using next generation sequencing analysis peripheral proteomics landscape Olink revealed lower variant allele frequency (VAF) at baseline, greater reduction VAF on treatment, hot macroenvironment associated independently. Our showed antitumor activity tislelizumab, cetuximab, tolerable safety profile WT Monotherapy checkpoint inhibitors has shown limited clinical (CRC). Here authors report results trial (anti-PD1) refractory CRC.

Language: Английский

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The efficacy and safety of suvemcitug, envafolimab, and FOLFIRI in microsatellite-stable or mismatch repair–proficient colorectal cancer: preliminary results of a phase 2 study

International Journal of Colorectal Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 21, 2025

Language: Английский

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